Screening Of Anti - Cerebral Ischemic Activity Of LA Series Compounds And Its Mechanism

Linarinic acid is a new quinazoline alkaloids isolated from the ethanol extract of the whole herb of L. vulgaris Mill. We used the PASS program to predict the activity of Linarinic acid. The result showed that the Linarinic acid had significant activity of stimulating cardiovascular system.In the present study, we investigated the effects of 35 LA compounds on MDA contents in vitro. The TBA test was used to measure MDA formed in peroxidizing lipid systems. Among these LA compounds,30 compounds had significant inhibitory effect with IC50 ranged from 0.1 to 18.0mM. Structure-activity relationship revealed that the biological activity were obviously enhanced after 7-halogen or 7-amino substitutions, while 7-nitro substitutions might decrease the activities. The activity of mostly S-configure is better than R-configure in LA compounds. Among the 30 LA compounds, screened 17 advantages of compounds configuration and 12 compounds had stronger inhibition than Linarinic acid and concentration-dependently reduced the content of MDA in vitro.Then, to investigate the protective effect of LA-20/21 on incomplete cerebral ischemia in mice, cerebral ischemia was produced by the bilateral carotid artery occlusion with vague nerves ligation (BCAO-VNL) and bilateral carotid artery occlusion (BCAO) in mice. Then, we detected the survival time and the content of MDA in BCAO-VNL and the survival time of natural death mice in 5 hours of BCAO. The results showed that LA-20/21 could effectively extend survival time of the BCAO-VNL, and significantly reduced the content of MDA in brain of mice; The LA-20 could effectively extend survival time of the BCAO in mice.In addition, to assay the effects of 35 LA compounds on platelet aggregation of rabbits induced by ADP in vitro, turbidimetric method were used to measure the maximum platelet aggregation rate. The results showed that most of LA compounds had no inhibition of platelet aggregation except LA-29, LA-16, LA-30 and LA-35.Based on above results, to investigate the antioxidant effect of LA compounds on SH-SY5Y neuroblostoma cells injury induced by hydrogen peroxide,17 advantages of LA compounds were selected to assay on cell viability by MTT measure. The results showed that 9 compounds could increase the cell viability and showed the neuroprotective effects on SH-SY5Y cells compared with model group.In conclusion, the primary study indicated that LA compounds showed alleviating cerebral ischemia. The mechanism may be related to eradiating free radical.